June 2 (Bloomberg) -- Dennis Prestholdt credits the past
three years of his life to Johnson & Johnson’s Zytiga, the first
prostate cancer pill to win U.S. marketing approval in a family
of treatments that offer new ways to stymie the male hormones
that fuel tumor growth.

Prestholdt, 67, a retired engineer at Honeywell
International Inc., began taking Zytiga in 2008 as part of a
clinical trial. On April 28, the drug was cleared for sale and,
within five years, may generate $2.1 billion a year, said Jami
Rubin, a Goldman Sachs Group Inc. analyst in New York.

The J&J drug may be a harbinger, said Eric Schmidt, a Cowen
& Co. analyst. Similar medicines from Medivation Inc. and Takeda
Pharmaceutical Co. will report study results this weekend at the
American Society of Clinical Oncology meeting in Chicago. If
approved, they would combine with Zytiga and other treatments to
boost the market for prostate cancer therapies to $5 billion by
2015 from less than $1 billion now, Schmidt said.

“It’s stunning how much innovation has taken place in the
last five to six years,” Schmidt said in a telephone interview.
“It is never a great time to be a prostate cancer patient, but
it sure beats a few years ago when the pipeline was barren.”

While these drugs don’t cure the disease, the therapies
give doctors options to help patients live longer, said Charles
Ryan, a medical oncologist and prostate cancer researcher at the
University of California, San Francisco.

Tripling Survival Time

“If you go back to 1985 and ask what happened to a guy
with advanced prostate cancer who went on hormone therapy, the
answer is he lived about 12 months,” said Ryan, who is treating
Prestholdt. Using treatments approved in the past year, “you
can probably triple that,” he said in an interview.

Medivation’s drug, called MDV3100, “has the potential to
really add to the mix,” Ryan said.

The medicine from the San Francisco-based company,
developed with Astellas Pharma Inc. of Tokyo, may win U.S.
approval by 2013 and reach annual sales of $1.7 billion by 2017,
said Howard Liang, a Leerink Swann & Co. analyst in Boston.

The Millennium unit of Osaka, Japan-based Takeda is testing
TAK700, a product similar to Zytiga, in late-stage trials that
may be completed by 2013 or 2014, Nancy Simonian, Millenium’s
chief medical officer, said in a telephone interview.

About 218,000 U.S. men are diagnosed with prostate cancer
and 32,000 die each year from the disease, according to the
American Cancer Society. If a tumor is confined to the prostate,
the walnut-sized gland between the bladder and urethra, patients
may seek surgery or radiation to eliminate it. Or they may do
nothing because a slow-growing prostate tumor may not alter an
older man’s life expectancy.

Cancer Spread

In about 15 percent of men with prostate tumors, the cancer
will spread, according to the National Cancer Institute. For
these patients, no cure exists. Treatments aim to keep the
testicles from producing testosterone and other male hormones
known as androgens, which prostate cancer cells use to grow.

One way is to surgically remove the testicles. Another
treatment is a form of chemical castration called androgen
deprivation using drugs such as Abbott Laboratories’ Lupron or
AstraZeneca Plc’s Casodex.

These drugs “always work, but over time the treatment
fails, usually after two years or sometimes longer,” said
Matthew Smith, an oncologist and prostate cancer specialist at
Harvard Medical School in Boston.

The effort to block testosterone fails when the adrenal
gland or the tumor begins making small amounts of androgen that
kick-start new cancer growth, Ryan said. In the past, there was
no way to stop that androgen.

New Theory

Zytiga from New Brunswick, New Jersey-based J&J changed the
thinking by targeting an enzyme called CYP17 that helps make
androgens outside the testicles. Stop it and you cut off a
tumor’s androgen “fuel supply,” Ryan said.

Hormone therapy kept Prestholdt’s illness in check for 10
years before his levels of PSA, a protein associated with
prostate cancer, began to climb, signaling the disease was again
on the march. He conducted research on the Internet and learned
about Ryan’s clinical trial of Zytiga, then known as abiraterone
acetate. He e-mailed the doctor, visited, and in early 2008
began taking the pill as part of the study.

Given to patients with advanced prostate cancer who had
stopped responding to standard hormone treatments and
chemotherapy, Zytiga boosted survival from 11 months to 15
months, a study found.

PSA Levels Plunge

Prestholdt and patients in a smaller trial received the
pill before getting chemotherapy and many got more benefit.
Within two months of starting treatment, Prestholdt’s PSA level
plunged to zero, where it remains 40 months later, Ryan said.

Medivation’s drug was discovered by researcher Charles
Sawyers at the University of California, Los Angeles. He found
what he calls the chief culprit in prostate cancer -- proteins
known as androgen receptors that sit on the surface of tumor
cells and act to switch on cancer-promoting processes.

“The androgen receptor is the business end of this whole
pathway,” Sawyers, who now works at Memorial Sloan-Kettering
Cancer Center in New York, said in a telephone interview. “It’s
an oncogene” -- a cancer-promoting gene -- “for prostate
cancer that turns on a whole repertoire of other genes.”

Sawyers and his team looked for a compound to block the
receptor. The result was the drug now known as MDV3100. Sawyers
told David Hung, Medivation’s chief executive officer and an old
medical school classmate, about his findings, and Hung licensed
the rights and put the medicine into clinical trials.

Early Studies

An early stage trial of 140 men showed that after 12 weeks
on the drug, PSA levels were cut in half in 62 percent of those
who hadn’t been treated with chemotherapy and 51 percent of
those who had, according to a company presentation in April.
Takeda’s experimental medicine reduced PSA levels by half or
more in as many as 63 percent of 96 men who hadn’t previously
received chemotherapy, according to an early study to be
presented at the cancer meeting.

MDV3100 acts on the most important driver of prostate cancer
growth, while Zytiga exercises an indirect effect, knocking down
testosterone levels to keep the androgen receptor from turning
on, Hung and Sawyers said. Having multiple treatments may
provide alternatives when tumors become resistant to one drug
and stop responding, Ryan said.

“If you have drugs that work on different mechanisms, you
can go from mechanism A to B to C and hit the cancer at three
different weak points, from different angles,” Ryan said.

J&J’s drug may boost blood pressure, lower potassium and
increase fluid retention, raising the risk of heart disease. To
reduce these risks, patients take it with steroids.

Prestholdt also manages side effects such as fatigue and
regular hot flashes normally associated with female menopause. A
thick, absorbent T-shirt and a sense of humor help, he said. So
does staying active.

“I’m basically enjoying my life at this point and hoping I
can keep going as long as I can,” Prestholdt said.